PB2346: ZUMA-24: A PHASE 2, OPEN-LABEL, MULTICENTER STUDY OF AXICABTAGENE CILOLEUCEL IN PATIENTS WITH RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA GIVEN WITH CORTICOSTEROIDS IN THE OUTPATIENT SETTING
Authors: Lori Leslie, Michael Tees, Ian W. Flinn, Tulio Rodriguez, John H. Baird, Abhinav Deol, Monica Mead, Carlos Bachier, Aaron P. Rapoport, Brian Mcclune, Daanish Hoda, Miguel-Angel Perales, Yan Zheng, Simone Filosto, Madison Davis1, Harry Miao, Jenny J. Kim, Olalekan O. Oluwole
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for the treatment of adults with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) after ≥2 lines of systemic therapy and for R/R LBCL within 12 months of first-line chemoimmunotherapy. Cohorts 1 and 2 of the ZUMA-1 study of axi-cel in refractory LBCL showed an objective response rate (ORR) of 83% (complete response [CR] rate, 58%), and Grade ≥3 cytokine release syndrome (CRS) and neurologic events (NEs) were experienced by 11% and 31% of patients, respectively, after ≥2 years median follow-up (Locke et al. Lancet Oncol. 2019). ZUMA-7 (Locke et al. N Engl J Med. 2022) examined axi-cel versus standard of care in patients with R/R LBCL after 1 line of prior therapy and showed efficacy (ORR, 84%; CR rate, 65%) and safety (Grade ≥3 CRS, 6%; Grade ≥3 NEs, 21%) consistent with ZUMA-1 Cohorts 1 and 2. Owing in part to this safety profile, most patients receive commercial axi-cel in an inpatient setting. ZUMA-1 Cohort 6, which evaluated whether improved safety outcomes were observed with prophylactic corticosteroids and earlier use of corticosteroids and/or tocilizumab to manage CRS and NEs, demonstrated no Grade ≥3 CRS and 18% Grade ≥3 NEs with high, durable response rates (ORR, 95%; CR rate, 80%) after ≥2 years median follow-up (Oluwole et al. ASH 2022. #705). Aims: To further advance safety management strategies with axi-cel, ZUMA-24, a Phase 2, open-label, multicenter study, will evaluate the safety and efficacy of axi-cel with prophylactic corticosteroid use in patients with R/R LBCL after 1 prior line of therapy in the outpatient setting. Methods: ZUMA-24 will enroll approximately 40 adult patients with histologically confirmed R/R LBCL who received adequate prior therapy (anti-CD20 monoclonal antibody and anthracycline-containing chemotherapy). Patients will undergo leukapheresis, followed by lymphodepleting chemotherapy (fludarabine/cyclophosphamide) and a single axi-cel infusion (2×106 CAR T cells/kg). Prior to axi-cel infusion on Day 0 and on Days 1 and 2, patients will receive prophylactic dexamethasone at a dose of 10 mg. Patients will undergo daily outpatient monitoring to manage AEs for ≥7 days after axi-cel infusion as set forth by institutional outpatient monitoring program. The primary endpoint is incidence and severity of CRS and NEs. Key secondary endpoints are time to onset and duration of CRS and NEs, rate and duration of hospitalization after axi-cel infusion due to AEs, and measures of efficacy including ORR, CR rate, duration of response, progression-free survival, and overall survival. Additional key inclusion criteria are Eastern Cooperative Oncology Group performance score 0-1 and adherence to prespecified institutional clinical monitoring requirements. Key exclusion criteria include >1 prior line of therapy for LBCL, prior stem cell transplant, and prior anti-CD19 or CAR T-cell therapy. Results: The study is open and actively accruing patients at sites in the United States (NCT05459571). Summary/Conclusion: ZUMA-24 will examine the safety and efficacy of axi-cel with prophylactic corticosteroid use in patients with R/R LBCL after 1 prior line of therapy in the outpatient setting. Keywords: Corticosteroids, CD19, CAR-T, Lymphoma